Abstract
The immune system is a complex network that acts to protect vertebrates from foreign microorganisms and carries out immunosurveillance to combat cancer. In order to avoid hyper-activation of the immune system leading to collateral damage tissues and organs and to prevent self-attack, the network has the intrinsic control mechanisms that negatively regulate immune responses. Central to this negative regulation are regulatory T (T-Reg) cells, which through cytokine secretion and cell interaction limit uncontrolled clonal expansion and functions of activated immune cells. Given that positive or negative manipulation of T-Regs activity could be utilised to therapeutically treat host versus graft rejection or cancer respectively, understanding how signaling pathways impact on T-Regs function should reveal potential targets with which to intervene. The phosphatidylinositol-3-kinase (PI3K) pathway controls a vast array of cellular processes and is critical in T cell activation. Here we focus on phosphoinositide 3-kinases (PI3Ks) and their ability to regulate T-Regs cell differentiation and function.
Keywords:
FOXOP3; Immune system; Lipid kinase; Naive T reg; PI3K; Phosphoinositide.
Copyright © 2020. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antineoplastic Agents, Immunological / therapeutic use
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology*
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Gene Expression Regulation, Neoplastic
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Humans
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Immunotherapy / methods
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Lymphocyte Activation
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Mice
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Neoplasms / drug therapy
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Neoplasms / genetics
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Neoplasms / immunology*
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Neoplasms / pathology
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / immunology*
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Phosphatidylinositols / immunology
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Phosphatidylinositols / metabolism
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Protein Subunits / antagonists & inhibitors
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Protein Subunits / genetics
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Protein Subunits / immunology*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Signal Transduction / drug effects
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Signal Transduction / immunology*
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / pathology
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Th17 Cells / drug effects
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Th17 Cells / immunology
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Th17 Cells / pathology
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Th2 Cells / drug effects
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Th2 Cells / immunology
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Th2 Cells / pathology
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Tumor-Associated Macrophages / drug effects
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Tumor-Associated Macrophages / immunology
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Tumor-Associated Macrophages / pathology
Substances
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Antineoplastic Agents, Immunological
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FOXP3 protein, human
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Forkhead Transcription Factors
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Phosphatidylinositols
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Protein Subunits
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Receptors, Antigen, T-Cell